Vanadate Induction of NF-kB Involves IkB Kinase B and SAPK/ERK Kinasa 1 in Macrophages

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Demers LM ; Ding M ; Lu Y ; Shi X ; Vallyathan V
• Description:
  The present studies investigated the signaling pathways of vanadate, a vanadium ion with +5 oxidation state, to activate NF-kappaB transcription factor, a pivotal regulator of inflammatory responses. Treatment of macrophages with vanadate results in the activation of both NF-kappaB and c-Jun N-terminal kinase (JNK). The activity of a recently identified cellular kinase, IkappaB kinase-beta (IKKbeta), was significantly elevated concomitant with the increased degradation of IkappaBalpha and enhanced NF-kappaB activity in cells exposed to vanadate. To determine whether the IKK pathway and JNK pathway are interconnected or bifurcate upon vanadate stimulation, cells were transfected with either a kinase inactive form of IKKbeta or a kinase inactive form of SAPK/ERK kinase 1 (SEK1). Inactive IKKbeta was able to block vanadate-induced degradation of IkappaBalpha, yet it was unable to influence the activation of JNK by vanadate. Conversely, blockage of JNK activation by transfection of a kinase-inactive form of SEK1 resulted in partially inhibition of vanadate-induced IkappaBalpha degradation. Both vanadate-induced degradation of IkappaBalpha and activation of JNK were potently inhibited by pretreatment of cells with N-acetylcysteine or dimercaprol. These results demonstrate that early activation of stress kinases or change of cellular redox states plays a key role in vanadate-induced activation of NF-kappaB and JNK. [Description provided by NIOSH]
• Subjects:
  Cardiovascular Diseases Cardiovascular System Energy Metabolism Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Carcinomas Cardiopulmonary-system-disorders In-vitro-studies Metabolites Particulates Pulmonary-system-disorders Vandium-compounds
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  274
• Issue:
  29
• NIOSHTIC Number:
  nn:20000956
• Citation:
  J Biol Chem 1999 Jul; 274(29):20307-20312
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dc061d7b15074b61724da6890dcfd29b5e2211a50e3d00b37c70db908ebbeb93fb704d7f86cfe2dbed2ba59da48db0e7dc0d88b56da0ac450915e564585f189b
• Download URL:
  https://stacks.cdc.gov/view/cdc/198270/cdc_198270_DS1.pdf
• File Type:
  [PDF - 280.43 KB ]